The primary aim of this study is to test the effects of excitation of ventral striatal circuitry via DBS (e.g. DBS-on versus DBS-off) on reward motivation. The investigators predict that stimulation will increase subject willingness to expend effort for rewards and facilitate motivation for reward learning. The investigators further predict that individual differences in the effects of DBS on reward motivation as will be associated with effects of DBS treatment on anhedonic symptoms.

The EEfRT is a multi-trial computer-based task that assess an individual's willingness to expend effort for the chance to earn monetary rewards. We will assess whether stimulation of the Ventral Capsule/Ventral Striatum has an effect on behavior by executing this task with the DBS system on and off.

This task is an additional reward task that assesses reward learning. We will assess whether stimulation of the Ventral Capsule/Ventral Striatum has an effect on behavior by executing this task with the DBS system on and off.

The study will take place at a clinical office in the CNY, and will consist of a single visit lasting up to 4 hours. Study staff will schedule a convenient time for patients to arrive, or the research visit may be paired with a regularly scheduled DBS programming visit. A member of the Division of Neurotherapeutics authorized to manipulate DBS programming will turn the device on and off during the study. The subject's therapeutic parameters of the DBS system will not be changed. The subject will be asked to complete four self-report questionnaires: the Temporal Experience of Pleasure questionnaire, the Chapman Anhedonia Questionnaire, the Perceived Stress Questionnaire (PSS) and the Mood and Anxiety Symptom Questionnaire (MASQ). Following these questionnaires, a member of the study staff will teach the subjects to perform the following tasks on the computer:

Effort Expenditure for Rewards Task (EEfRT) To measure motivation to work for rewards, we will use the Effort Expenditure for Rewards Task (EEfRT or "effort"). The EEfRT is a multi-trial computer-based task that assess an individual's willingness to expend effort for the chance to earn monetary rewards developed by Michael Treadway and David Zald at Vanderbilt University (Treadway et al., 2009). On each trial, subjects are given an opportunity to choose between two different task difficulty levels in order to obtain monetary rewards. For all trials, subjects must make repeated manual button presses in a set period of time. Each button press raises the level of a virtual "bar" viewed onscreen by the subject. Subjects will be eligible to win the money allotted for each trial if they are able to raise the bar to the "top" within the prescribed time period. This button-press task has two levels of difficulty: referred to henceforth as the 'hard task' or 'easy task'. Successful completion of hard task trials requires the subject to make 100 button presses, using the non-dominant pinky finger within 30 seconds, while successful completion of easy task trials requires the subject to make 30 button presses, using the dominant index finger within 10 seconds.

For easy task choices, subjects are eligible to win the same amount on each trial if they successfully complete the task. For hard task choices, subjects are eligible to win an amount that varies per trial. Subjects are not guaranteed to win the stated reward if they complete the task; some trials are 'win' trials, in which the subject receives the stated reward amount, while others are 'no win' trials, in which the subject receives no money for that trial. To help subjects determine which trials are more likely to be win trials, subjects are provided with probability cues at the beginning of each trial. Trials have three levels of probability: 88% probability of being a win trial, 50% and 12%. There are equal proportions of each probability level across the experiment. Each level of probability appears once in conjunction with each level of reward value for the hard task.

At the beginning of the task, subjects are provided with a detailed set of instructions, and an opportunity to play 4 practice trials. Subjects are then told that they will have twenty (20) minutes to play as many trials as they can. Easy Task choices take approximately 15 seconds, whereas Hard Task choices take approximately 30 seconds. Therefore, the number of trials that the subject is able to play will depend in part on the choices that she makes. This means that making more Hard Task trials early-on in the experiment will result in fewer trials total, which may mean that the subject does not get a chance to play high-value, high-probability trials that could appear towards the end of the playing time. This trade-off is explained clearly to the subject. The goal of this trade-off is to ensure that neither a strategy of always choosing the easy or the hard option can lead to optimal performance on the task. Moreover, the complexity of variables (with varying monetary reward levels, probability, and loss of time for future trials), does not lend itself to a formal calculation of an optimal response selection, forcing Subjects to make a relatively rapid decision, that we believe taps individual differences in the willingness to expend effort for a given level of expected reward value.

At the end of the task, two trials are randomly selected that will be added to the subject's compensation as a reward incentive. Subjects therefore may earn additional funds in incentive performance compensation each time they complete the EEfRT.

Clock Task The "clock task" is an additional reward task that assesses reward learning developed by Michael Frank and colleagues (Moustafa et al., 2008; Frank et al., 2009). For this task, participants observe a clock arm that completes a revolution over the course of 5 seconds, and participants are instructed to press a key to stop the clock at any time in an attempt to win points. The amount of points won varies depending on RT, and participants must use trial-and-error strategies to learn when to stop the clock so as to maximize points received. To prevent subjects form explicitly learning reward values associated with a specific location on the clock face, reward values at any given point along the clock face are randomized within +/- 5 points. At the end of the task, subjects may redeem points for a small amount of additional compensation, each time they complete the task. This task takes approximately 15 minutes to complete.

30 minutes after turning OFF DBS stimulation, participants will either remain in the OFF condition or will have the DBS turned ON, depending on their counter-balanced condition assignment. Subject assignment will alternate sequentially. Subjects will complete the tasks above in the first condition. Following task completion, subjects will have DBS stimulation turned OFF or ON (again, depending on condition assignment). After 30 minutes, participants will complete the same tasks in the second condition. Following retesting, participants that were in the OFF condition will return to ON DBS stimulation.

We will be using the implanted pulse generator, so it is not possible to deliver an unsafe current. Because we are not changing the therapeutic parameters of stimulation, subjects should not experience and adverse side effects. The computer will register the subject's performance.

Electroencephalography recordings (EEG) will be acquired during performance of the aforementioned tasks. Continuous EEG data will be sampled at a maximum of 1024Hz using a 64-electrode cap. Eye movement artifacts will be assessed using bipolar electrodes.

Eligibility

Ages Eligible for Study:

18 Years to 70 Years

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

Deep brain stimulator implantation performed at least three months prior to study

Exclusion Criteria:

Subjects unable to visualize stimulus objects with correction

Dementia or other known cognitive deficit

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01590862